CN1942195A - Methods of treating hepatocellular carcinoma with DENSPM - Google Patents

Methods of treating hepatocellular carcinoma with DENSPM Download PDF

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Publication number
CN1942195A
CN1942195A CNA2005800109395A CN200580010939A CN1942195A CN 1942195 A CN1942195 A CN 1942195A CN A2005800109395 A CNA2005800109395 A CN A2005800109395A CN 200580010939 A CN200580010939 A CN 200580010939A CN 1942195 A CN1942195 A CN 1942195A
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CN
China
Prior art keywords
denspm
treatment
hydrochlorate
patient
dosed administration
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Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CNA2005800109395A
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Chinese (zh)
Inventor
D·戴维森
R·伯格伦
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Genzyme Corp
University of Florida Research Foundation Inc
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Genzyme Corp
University of Florida Research Foundation Inc
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Publication of CN1942195A publication Critical patent/CN1942195A/en
Pending legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/785—Polymers containing nitrogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Abstract

The disclosure provides methods for treating hepatocellular carcinoma. The methods include administering to a subject an effective amount of DENSPM to treat the hepatocellular carcinoma.

Description

Method with DENSPM treatment hepatocarcinoma
The application requires the U.S. Patent application No.60/561 to submission on April 12nd, 2004, and 438 priority, this application are incorporated the application into as a reference in full.
Technical field
The present invention relates to the application of DENSPM in the method for treatment hepatocarcinoma.
Background technology
(HCC) is more rare in developed country for hepatocarcinoma.Yet the about million people of its annual influence represents the whole world the 5th kind of most common tumor (Alsowmely, A.M. etc. (2002) Aliment Pharmacol.Ther.16 (1): 1-15).ACS estimates, diagnoses out 17,300 new hepatocarcinoma cases in the U.S. in 2003, and wherein about 2/3 is HCC.In same year, expection 14,400 people died from hepatocarcinoma, have reflected the method for also successfully not treating these tumors.
So far, except the therapeutic excision, the treatment of HCC is very little to the influence of survival rate.Unfortunately, about 90% HCC patient suffers from unresectable HCC.In addition, even after the patient who suffers from resectable HCC is as hepatectomy that may radical-ability, these patients' 70% produce new HCC in the cirrhosis residue, and usually betide in the liver transplantation after the orthotopic liver transplantation.The method of other treatment HCC, for example intralesional injection Ethanol Method, chemoembolization art, radio-frequency (RF) ablation, cryosurgery operation and radiation method are succeedd in the patient colony that picks out.But the effectiveness of these methods does not obtain sure affirmation as yet.Percutaneous has all shown limited success at intralesional injection ethanol and transarterial chemoembolization art, but is not the danger that does not have serious side reaction.X-ray therapy is not alternative usually, because liver is extremely responsive to radiation.Responsiveness for the systemic chemotherapy of HCC is very poor without exception, and therefore general only the reservation given the not patient of treatability excision.
Up to now, all same poor effect of systemic therapy of HCC, and do not have chemotherapeutics independent or that combine with other treatment demonstrating any improvement (Fuchs, C.S etc. (2002) Cancer 94 (12): 3186-91) aspect the survival rate.In addition, most of HCC patients suffer from more basic hepatopathy, thus they to stand the ability of chemotherapy regimen or operative treatment usually weakened.
Since alternative Therapeutic Method poorness, obvious new departure that needs the treatment hepatocarcinoma.
Brief summary of the invention
The invention provides the method for treatment hepatocarcinoma.An others part of the present invention will state in the following description that a part will obtain understanding by this explanation, and a part can be understood by practice of the present invention.
In an embodiment, the invention provides the method for treatment hepatocarcinoma, comprise DENSPM or its pharmaceutically useful salt to patient's administering therapeutic effective dose of this treatment of needs.DENSPM or its pharmaceutically useful salt can intravenouss, dispenser in intralesional or the liver.
In some embodiments of the present invention, the patient who suffers from unresectable hepatocarcinoma obtains medical treatment.In other embodiments, that treatment is the patient who suffers from the hepatocarcinoma of other Therapeutic Method refractory.
In some embodiments of the present invention, take DENSPM once a day.In other embodiments, took 2,3,4 or DENSPM of more times number in one day, perhaps with infusion form continuous administration.
In some embodiments of the present invention, with about 30-300mg/m 2The dosage range of (containing) is used DENSPM.In these embodiments, have some with 30,60,90,120,150,180,210,240,270,300mg/m 2Dosage or the dosage of therebetween any increment use DENSPM.For example, can adopt the dosage that in following scope, changes to take DENSPM:30-60mg/m 2, 90-120mg/m 2, 120-150mg/m 2, 150-180mg/m 2, 180-210mg/m 2, 210-240mg/m 2, 240-270mg/m 2, and 270-300mg/m 2
In some embodiments of above-mentioned the present invention, take DENSPM itself.In other above-mentioned embodiments, take the officinal salt of DENSPM.Preferred DENSPM officinal salt comprises the DENSPM hydrochlorate.
In some embodiments of the present invention, the patient to the method for not accepting any other treatment HCC uses DENSPM.In some these class embodiments, the patient accepts the method for other treatment HCC, but any other cancer therapy drug of the HCC that do not receive treatment.
Other purpose of the present invention and an advantage part will state in explanation subsequently that from explanation obviously as seen a part will perhaps can be understood by practice of the present invention.These purposes of the present invention and advantage will be by the key element specifically noted in claims and combinations and are familiar with and realize.
Should understand, above general description and following detailed description all are example and indicative, are not to claimed restriction of the present invention.
The description of embodiment
For the present invention can more easily be understood, some terms have been defined herein.Definition is in addition then stated in detailed Description Of The Invention.
Term " hepatocarcinoma " and " HCC " use in this article interchangeably, refer to the cancer that takes place by as the hepatocyte of the main cell type of liver.
Term used herein " DENSPM " is meant N ', N, and " the nor-spermine of diethyl, it is N, N '-two [3-(ethylamino) propyl group]-1,3-propane diamine.Unless special in addition explanation, term DENSPM comprises DENSPM and any pharmaceutically useful salt thereof.The salt of a kind of preferred DENSPM is N, N '-two [3-(ethylamino) propyl group]-1,3-propane diamine four hydrochlorates.DENSPM is a kind of known dysfunction polyamine analogs, can prepare with known method.For example, Bergeron is in U.S. Patent No. 5,091, and 596,5,342,945 and 5,866,613 and J.Med.Chem.1988,31 (6): described synthetic such as polyamines such as DENSPM among the 1183-90, above-mentioned each document all is incorporated herein by reference.
Term " pharmaceutically useful salt " comprises the salt that can use to the patient safely when using in this article.The officinal salt of preferred DENSPM includes but not limited to the salt that is equipped with from following processed with acid: hydrochloric acid, hydrobromic acid, sulphuric acid, nitric acid, phosphoric acid, maleic acid, salicylic acid, p-methyl benzenesulfonic acid, tartaric acid, citric acid, methane-disulfonic acid, formic acid, malonic acid, succinic acid, naphthalenedisulfonic acid and benzenesulfonic acid.Pharmaceutically useful salt also can be from the metal such as alkali metal or alkaline-earth metal, for example sodium, potassium and calcium, magnesium and zinc preparation.Pharmaceutically useful salt also includes but not limited to the salt with acid formation, sulfate for example, pyrosulfate, disulfate, sulphite, bisulfites, phosphate, dibasic phosphate, dihydric phosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, propionate, caprate, caprylate, acrylates, formates, isobutyrate, caproate, enanthate, propiolate, oxalates, malonate, succinate, suberate, sebacate, fumarate, maleate, 2-butyne-1, the 4-diacid salt, 3-hexin-2, the 5-diacid salt, benzoate, chloro benzoate, hydroxy benzoate, methoxybenzoic acid salt, phthalate, xylenesulfonate, phenylacetic acid salt, phenpropionate, benzenebutanoic acid salt, citrate, lactate, hippurate, beta-hydroxy-butanoic acid salt, hydroxyl acetate, tartrate, mesylate, propane sulfonic acid salt, naphthalene-1-sulfonate, naphthalene-2-sulfonic acid salt and mandelate.
Term " treatment ", " Therapeutic Method " and cognate thereof are meant existing treatment of conditions and prevention or the measure of preventing property.Need therapist to comprise to have suffered from the individual and dangerous of HCC or finally may suffer from the individuality of HCC.
Term " effective dose ", " effectively quantity ", " effective dose " and cognate thereof when using in this article, are meant treatment and/or the beneficial DENSPM quantity of control HCC.Effective dose can or as be shown in the examplesly be determined with method well known in the art.In an embodiment of the present invention, effective quantity of treatment hepatocarcinoma is for HCC growth of tumor among the inhibition patient or reduces the necessary quantity of its size.When the patient uses, the significant figure amount depends on the order of severity of HCC; Concrete patient parameter, health for example, stature and weight; The concurrent treatment that may carry out; Therapeutic frequency; And medicining mode.Follow treatment, if any, also can influence effective dose.Usually the scope of preferably using from this treatment level until certain dosage of the highest dosis tolerata.
" the highest dosis tolerata " or " MTD ", when using in this article, be meant adult patients can safety clothes with so that the maximum DENSPM dosage of treatment HCC.The highest dosis tolerata can only can be determined with normal experiment by those skilled in the art.
Term " treatment level " is meant when using in this article effective minimum DENSPM concentration on the concrete patient treatment.Certainly, those of skill in the art will recognize that treatment level and MTD can become with the individuality of being treated and symptom and the order of severity.For example, concrete patient's age, body weight and can influence the curative effect of treatment with regard to Biography of Medical Figures.Competent doctor will consider these factors and adjusts application method and need not too much experiment, to guarantee that dosage can reach desirable therapeutic effect.It shall yet further be noted that how and when clinicist and/or attending doctor can know that response according to concrete patient is interrupted, adjusts and/or finishes and treat.
Term administering " and cognate, when using in this article, be meant the action that gives patient DENSPM.Many kinds of drug delivery routes can be for adopting.Concrete route of administration will depend on the order of severity and other factor of HCC, for example, and to doctor and/or patient's convenience.The general available medically acceptable any application method of method of the present invention is implemented, and this means can adopt the DENSPM that produces valid density and do not cause any way of unacceptable adverse effect clinically.That insecticide-applying way comprises is oral, per rectum, Sublingual, part, buccal, per nasal, transvaginal, transdermal and parenteral route.That " non-intestinal " used herein speech comprises is subcutaneous, intravenous, inject, route of administration such as intraperitoneal, intramuscular and infusion.Preferred intravenous administration approach.
Term " object " and " patient " are used interchangeably in this article, are meant people, non-human primates, Canis familiaris L., cat, horse, sheep, goat, cattle, rabbit, pig and rodent.Preferred human patients.
When using in this article, term " unresectable hepatocarcinoma " is meant the operation method that can not use standard, for example the HCC of partial hepatectomy or orthotopic liver transplantation art healing.
When using in this article, term " refractory " is meant a kind of disease that treatment is had resistance, for example HCC.The patient who suffers from the HCC of other Therapeutic Method refractory comprises the standard method for treatment HCC, and for example intralesional injection ethanol, chemoembolization art, radio-frequency (RF) ablation method, first stage operation, radiotherapy or chemotherapy do not produce the patient of positive response.
Term " pharmaceutically useful carrier " when using in this article, is meant to be fit to one or more compatible solids or liquid filler, diluent or the encapsulating substance that the patient takes.A kind of organic or inorganic, natural or synthetic composition represented in " carrier " speech, and active component DENSPM is with it in conjunction with so that use.
Term " pharmaceutical composition " and " pharmaceutical preparation " are used interchangeably in this article, refer to the DENSPM with pharmaceutically useful carrier combinations.Can randomly in pharmaceutical preparation, add excipient and/or adjuvant.The DENSPM preparation can provide with unit dosage forms easily, and the preparation of available pharmaceutical field known method.The preferred preparation that is fit to intravenous administration.Because dissolubility is higher, DENSPEM can be dissolved in the sterilized water (WFI) of injection with its hydrochloride form.A kind of like this solution can be packed in each dosage bottle and lyophilization, in order to reconstituting in the future solution and using.
The example of suitable moisture and non-water excipient comprises water, ethanol, polyhydric alcohol (for example glycerol, propylene glycol, Polyethylene Glycol etc.), oils, injectable organosilane ester and their mixture.Suitable mobility can keep by for example using surfactant.
Can also contain adjuvant in the compositions, for example, antiseptic, wetting agent, emulsifying agent and dispersant.By adding various antibiotic and/or antifungal, for example, p-Hydroxybenzoate, methaform, phenol, sorbic acid etc. can stop action of microorganisms.May also wish in compositions, to add isotonic agent, for example saccharide, sodium chloride etc.
For parenterai administration, for example intravenous administration can be mixed with isoosmotic suspension, solution or emulsion with containing DENSPM, and can contain preparaton in oil base or water base excipient, for example suspends, stablizes and/or dispersant.Or compositions can be made into dried form, and for example powder, crystal or cryodesiccated solid are used for before use and liquid (for example sterile pyrogen-free water or isotonic saline solution) reconstruct.They can be provided in aseptic ampoule bottle or the bottle standby.
The anticancer therapy medicine usually with the chemotherapy of other type, comprise being used in combination other chemotherapeutics.In an embodiment preferred, use DENSPM to the HCC patient who does not accept other any cancer therapy drug.These patients can randomly accept other anticancer therapy, for example X-ray therapy.
The embodiment example has illustrated an embodiment of the present invention from DENSPM to HCC patient that use, and how to determine therapeutic dose and the highest tolerance.
According to research and practice of the present invention disclosed herein to description, other embodiment of the present invention will be conspicuous for those skilled in the art.Description and embodiment just are used for example explanation, and real scope and spirit of the present invention are then pointed out by following claim.
Embodiment
Embodiment 1: therapeutic scheme
Be defined as first day of treatment on the 1st day.Following baseline estimate generally carried out in taking between the DENSPM for the first time at the 1st day: physical examination, vital sign, laboratory test (for example, hematology, blood coagulation, chemistry and urinalysis), duty (Karnofsky), adverse events monitoring and the medication monitoring of following.
A treatment cycle is grown 28 days.In the cycle 1, the patient in all 1-week 3-week 5 or all 2-4-week 6 (for example the 1st, 3,5,8,10 and 12 day) in week, accepts DENSPM with the form of 15 minutes single intravenous infusions 3 times weekly in preceding 12 days of this cycle.After treatment in the 12nd day, before next treatment cycle of beginning, the patient has 16 days and does not carry out the DENSPM treatment.
In the 1st and the 2nd week of each treatment cycle, the schedule according to all 1-week 3-weeks 5 or all 2-4-week 6 in week carries out the DENSPM treatment on outpatient's basis.The extraction proper dosage also is diluted in the 50mL normal saline solution, and be infused in peripheral vein angular vein in inferior to 15 minutes every day 1.After using DENSPM, the patient stays outpatient service and observed 90 minutes.Write down vital sign before leaving.Height and ideal weight are used for the computer chart area.For the male, ideal weight is defined as 50Kg+2.3Kg * (highly surpassing 60 inches inch number).For the women, ideal weight is defined as 45.5Kg+2.3Kg * (highly surpassing 60 inches inch number).For highly being 60 inches or lower individuality, ideal weight is defined as 50Kg (male) or 45.5Kg (women).
If the treatment schedule is interrupted,, just fill the dosage of loss, so that finish the 6 complete dosage treatment cycles as long as the postponement of treatment is no more than 5 days.The beginning of next treatment cycle generally is no earlier than 21 days after medication last time, in week 1 or weeks 2 beginning.If the patient can not satisfy the recovery condition before next treatment cycle of beginning fully, then next treatment cycle is postponed and being carried out, and the patient is reappraised after 7 days in this situation.The beginning of next treatment cycle can be postponed at most 14 days so that can recover fully from toxicity.Anyly do not satisfy this recovery standard and patient that can not begin treatment in 14 days treatment dates of regulation, can stop treatment.
Usually, in treatment cycle, carry out kidney and liver function test, analyzing blood, monitoring side reaction, and the Drug therapy of monitoring companion row.Kidney and liver function test can be in preceding 12 days of this cycle, the patient who treats for receiving treatment in 3-week 5 in all 1-weeks is in all 3-week 5-week 1-3-weeks 5 in week, for the patient who receives treatment in 4-week 6 in all 2-week in all 4-week 6-week 2-4-weeks 6 (for example the 3rd, 5,8,10,12 day) in week, after treatment, carry out, and carry out once (for example 15-19 days) in the 3rd week in this cycle.Can carry out extra test for following the tracks of any freak result.Hemanalysis can carry out in 5/ week 6 of week (the 10th day) in the 2nd week, and carried out once (for example 15-19 days) in the 3rd week in this cycle.Can carry out extra test to follow the tracks of any freak result.If observe H﹠H significance reduction clinically taking place, then can carry out the feces guaiac test.Usually in 28 day cycle, monitored the Drug therapy of adverse events and companion's row always.Because known DENSPM can the of short duration and serum creatinine level that reversibly raises, should be careful when other nephrotoxicity agent and DENSPM share.
All and the relevant toxicity of treatment except kreatinin, all returned to before beginning even cycle 2,4 and 6≤grade 1 or patient's baseline usually.Surpass or equal the patient of 1.5 * ULN (upper limit of normal value) for serum creatinine, treatment kept 14 days at most usually, recovered up to kreatinin.For these patients, as described below, additional dose generally reduces 25%, and acceptable dose does not progressively rise again.
Usually carry out the recovery situation of following safety evaluation: physical examination, vital signs and laboratory test with (perhaps, except life is accused of, within 7 days before first treatment in this cycle day) before judging medication.Can accept the treatment of following one-period according to the patient of the suitable treatment of above-mentioned recovery standard.The patient can accept 1,2,3,4,5,6,7,8,9,10 or more multiply periodic treatment.
Embodiment 2:DENSPM preparation
DENSPM can cryodesiccated powder type supply, for example is packaged in the 10mL clear glass bottle that 215mg is housed.This lyophilized powder can be prepared as follows.The DENSPM hydrochlorate is dissolved in formation 5% solution among the aseptic WFI.The pH of this solution is adjusted to 2N NaOH is preferably about 5.8-6.2, most preferably be 6.0.Get this solution of 4.3mL under aseptic condition in 0.45 and 0.22 micron filter membrane of Millipak (R) is packed vial into, lyophilization then.The DENSPM of this form is physics and chemically stable when at room temperature storing.DENSPM and 4.3mL water for injection (USP) reconstruct.The solution that forms contains the DENSPM of 50mg/mL, at room temperature is chemistry and physically stable until about 96 hours.When further in the 50mL normal saline, diluting, when the mixture of formation is deposited under room temperature chemistry and physically stable.After the reconstruct, this medicine generally used in 8 hours, because of it does not contain antiseptic.

Claims (30)

1. method for the treatment of hepatocarcinoma is comprising DENSPM or its pharmaceutically useful salt the object of needs treatment used to treating the effective quantity of this hepatocarcinoma.
2. the process of claim 1 wherein that this hepatocarcinoma is unresectable.
3. the process of claim 1 wherein that this hepatocarcinoma is that other Therapeutic Method refractory is healed.
4. the process of claim 1 wherein that DENSPM takes once every day.
5. the process of claim 1 wherein the DENSPM intravenous administration.
6. the method for claim 5, wherein DENSPM with about 30 to about 300mg/m 2Dosed administration.
7. the method for claim 6, wherein DENSPM with about 30 to about 60mg/m 2Dosed administration.
8. the method for claim 6, wherein DENSPM with about 60 to about 90mg/m 2Dosed administration.
9. the method for claim 6, wherein DENSPM with about 90 to 120mg/m 2Dosed administration.
10. the method for claim 6, wherein DENSPM with about 120 to 150mg/m 2Dosed administration.
11. the method for claim 6, wherein DENSPM with about 150 to 180mg/m 2Dosed administration.
12. the method for claim 6, wherein DENSPM with about 180 to 210mg/m 2Dosed administration.
13. the method for claim 6, wherein DENSPM with about 210 to 240mg/m 2Dosed administration.
14. the method for claim 6, wherein DENSPM with about 240 to 270mg/m 2Dosed administration.
15. the method for claim 6, wherein DENSPM with about 270 to 300mg/m 2Dosed administration.
16. the process of claim 1 wherein and use the DENSPM hydrochlorate to the patient.
17. the method for claim 16 is wherein used the DENSPM hydrochlorate to patient's intravenous.
18. the method for claim 17, wherein with about 30 to about 300mg/m 2Dosage use the DENSPM hydrochlorate.
19. the method for claim 18, wherein with about 30 to about 60mg/m 2Dosage use the DENSPM hydrochlorate.
20. the method for claim 18, wherein with about 60 to about 90mg/m 2Dosage use the DENSPM hydrochlorate.
21. the method for claim 18 is wherein with 90-120mg/m 2Dosage use the DENSPM hydrochlorate.
22. the method for claim 18 is wherein with 120-150mg/m 2Dosage use the DENSPM hydrochlorate.
23. the method for claim 18 is wherein with 150-180mg/m 2Dosage use the DENSPM hydrochlorate.
24. the method for claim 18 is wherein with 180-210mg/m 2Dosage use the DENSPM hydrochlorate.
25. the method for claim 18 is wherein with 210-240mg/m 2Dosage use the DENSPM hydrochlorate.
26. the method for claim 18 is wherein with 240-270mg/m 2Dosage use the DENSPM hydrochlorate.
27. the method for claim 18 is wherein with 270-300mg/m 2Dosage use the DENSPM hydrochlorate.
28. hepatocellular method of treatment, comprising the object of needs treatment is used a therapeutic scheme of 28 days, this scheme is included in used DENSPM or its officinal salt to this treatment target on the 1st, 3,5,8,10 and 12 day, did not use SENSPM in 16 days subsequently.
29. the method for claim 28, wherein DENSPM uses with the form of DENSPM hydrochlorate.
30. the method for claim 29, wherein this therapeutic scheme repeats 1,2,3,4 or 5 time.
CNA2005800109395A 2004-04-12 2005-04-12 Methods of treating hepatocellular carcinoma with DENSPM Pending CN1942195A (en)

Applications Claiming Priority (2)

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US60/561,438 2004-04-12

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US5342945A (en) * 1986-12-02 1994-08-30 University Of Florida Research Foundation, Inc. Anti-neoplastic, anti-viral or anti-retroviral spermine derivatives
US5091596A (en) * 1990-12-20 1992-02-25 Univ. Of Va. Alumni Patents Foundation Method for producing chiro-inositol
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